Hirsute or Hairless? Two Proteins May Spell the Difference
Autor: | Colin Jamora, Elaine Fuchs, Pedro Lee, Ryoichi Hosokawa, Pawel Kocieniewski, Mohamad Azhar, Yang Chai |
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Rok vydání: | 2004 |
Předmět: |
Cell signaling
Time Factors Transcription Genetic QH301-705.5 MAP Kinase Signaling System Blotting Western Morphogenesis Down-Regulation Mice Transgenic Cell Communication Development Biology Epithelium General Biochemistry Genetics and Molecular Biology Mice Transforming Growth Factor beta2 Transforming Growth Factor beta medicine Animals Biology (General) Transcription factor Cell Proliferation Skin General Immunology and Microbiology Reverse Transcriptase Polymerase Chain Reaction Cadherin General Neuroscience Gene Expression Regulation Developmental Cell Biology Transforming growth factor beta Mus (Mouse) Cadherins Hair follicle Immunohistochemistry Cell biology Hair follicle morphogenesis medicine.anatomical_structure biology.protein Snail Family Transcription Factors Signal transduction General Agricultural and Biological Sciences Hair Follicle Research Article Signal Transduction Transcription Factors |
Zdroj: | PLoS Biology PLoS Biology, Vol 3, Iss 1, p e11 (2005) |
ISSN: | 1545-7885 |
Popis: | In a common theme of organogenesis, certain cells within a multipotent epithelial sheet exchange signals with their neighbors and develop into a bud structure. Using hair bud morphogenesis as a paradigm, we employed mutant mouse models and cultured keratinocytes to dissect the contributions of multiple extracellular cues in orchestrating adhesion dynamics and proliferation to shape the cluster of cells involved. We found that transforming growth factor β2 signaling is necessary to transiently induce the transcription factor Snail and activate the Ras-mitogen-activated protein kinase (MAPK) pathway in the bud. In the epidermis, Snail misexpression leads to hyperproliferation and a reduction in intercellular adhesion. When E-cadherin is transcriptionally down-regulated, associated adhesion proteins with dual functions in signaling are released from cell-cell contacts, a process which we demonstrate leads to Ras-MAPK activation. These studies provide insights into how multipotent cells within a sheet are stimulated to undergo transcriptional changes that result in proliferation, junctional remodeling, and bud formation. This novel signaling pathway further weaves together the web of different morphogens and downstream transcriptional events that guide hair bud formation within the developing skin. The study of hair follicle morphogenesis provides insights into how cells within a sheet can be triggered to proliferate, remodel, and form buds - a recurring theme in development |
Databáze: | OpenAIRE |
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